The aim of this proposal is to test the hypothesis that viral infections are associated with development of anti-virus antibodies cross-reacting with antigens present in cells of the CNS of normal animals. The possibility of such autoreactivity will be studied in vitro and in vivo using as a model mice spontaneously infected with Theiler's virus. The in vitro studies will be based on the isolation and characterization of antigens from uninfected human cells, cross-reacting with monoclonal Ab to purified measles virus or measles-infected cell lysates. The binding of monoclonal Ab to normal or infected cells will be established by immunofluorescence and immunoelectron microscopy, using the immunoperoxidase bridge technique or the immunocolloidal gold technique. These latter studies will be performed by Dr. Peter Lampert. Binding the monoclonal Ab will be performed by immunoprecipitation, Western blot analysis, involving separation of antigenic fractions in SDS gel, electrophoresis, reaction with monoclonal Ab, and identification of the reactive proteins with 123 I-labeled anti-mouse IgG; two dimensional gel separation; and high pressure liquid chromatography.